Preferential repair of DNA damage on the transcribed strand of the human metallothionein genes requires RNA polymerase II.

To examine the possible role of transcription in directing repair of DNA damage in active genes, we compared repair of UV- and aflatoxin B1-induced damage on each strand of the human metallothionein (hMT) genes. Repair on the transcribed strand of an active hMT gene occurs at least 3 times faster than that on its nontranscribed strand. Both strands of inactive genes and both strands of a regulatory region 5' to an active gene are not repaired at this faster rate. Inducing higher levels of transcription with dexamethasone selectively increased the rate of repair on only the transcribed strand of the induced gene, while treatment of cells with alpha-amanitin eliminated the strand-selective repair. These results demonstrate that repair on the transcribed strand of a gene is independent of repair on the nontranscribed strand and that the transcriptional complex plays a role in directing repair to the transcribed strand of active genes.